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1.
Artigo em Inglês | MEDLINE | ID: mdl-38950522

RESUMO

Better infection control will accelerate wound healing and alleviate associated healthcare burdens. Traditional antibacterial dressings often inadequately control infections, inadvertently promoting antibacterial resistance. Our research unveils a novel, dual-functional living dressing that autonomously generates antibacterial agents and delivers electrical stimulation, harnessing the power of spore-forming Bacillus subtilis. This dressing is built on an innovative wearable microbial fuel cell (MFC) framework, using B. subtilis endospores as a powerful, dormant biocatalyst. The endospores are resilient, reactivating in nutrient-rich wound exudate to produce electricity and antibacterial compounds. The combination allows B. subtilis to outcompete pathogens for food and other resources, thus fighting infections. The strategy is enhanced by the extracellular synthesis of tin oxide and copper oxide nanoparticles on the endospore surface, boosting antibacterial action, and electrical stimulation. Moreover, the MFC framework introduces a pioneering dressing design featuring a conductive hydrogel embedded within a paper-based substrate. The arrangement ensures cell stability and sustains a healing-friendly moist environment. Our approach has proven very effective against three key pathogens in biofilms: Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus demonstrating exceptional capabilities in both in vitro and ex vivo models. Our innovation marks a significant leap forward in wearable MFC-based wound care, offering a potent solution for treating infected wounds.

2.
Biomed Mater ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976990

RESUMO

Wound healing is a critical but complex biological process of skin tissue repair and regeneration resulting from various systems working together at the cellular and molecular levels. Quick wound healing and the problems associated with traditional wound repair techniques are being overcome with multifunctional materials. Over time, this research area has drawn significant attention. Metal-organic frameworks (MOFs), owning to their peculiar physicochemical characteristics, are now considered a promising class of well-suited porous materials for wound healing in addition to their other biological applications. This detailed literature review provides an overview of the latest developments in MOFs for wound healing applications. We have discussed the synthesis, essential biomedical properties, wound-healing mechanism, MOF-based dressing materials, and their wound-healing applications. The possible major challenges and limitations of MOFs have been discussed, along with conclusions and future perspectives. This overview of the literature review addresses MOFs-based wound healing from several angles and covers the most current developments in the subject. The readers may discover how the MOFs advanced this discipline by producing more inventive, useful, and successful dressings. It influences the development of future generations of biomaterials for the healing and regeneration of skin wounds.

3.
Future Sci OA ; 10(1): FSO921, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827799

RESUMO

Aim: Here, an innovative kind of antibacterial nanocomposite film is developed by incorporating graphene oxide and zinc oxide into chitosan matrix. Materials & methods: Our dressing was fabricated using the solution casting method. Fourier transform infrared spectra and TGA-DTG clearly confirmed the structure of film dressing. Results & conclusion: Our results showed the tensile strength and elongation at the break of the films were 20.1 ± 0.7 MPa and 36 ± 10%, respectively. Our fabricated film could absorb at least three-times the fluid of its dry weight while being biocompatible, antibacterial, non-irritant and non-allergic. In addition, it accelerated the healing process of infected wounds by regulating epithelium thickness and the number of inflammatory cells, thus it may be useful for direct application to damaged infected wounds.


In this study, an innovative kind of antibacterial nanocomposite film is developed by incorporating graphene oxide and zinc oxide into chitosan matrix. Our antibacterial wound dressing was fabricated using the solution casting method. Our fabricated film could absorb at least three-times the fluid of its dry weight while being biocompatible, antibacterial, non-irritant and non-allergic. In addition, our film accelerated the healing process of infected wounds by regulating epithelium thickness and the number of inflammatory cells. thus it may be useful for direct application to damaged infected wounds.

4.
Int J Biol Macromol ; 271(Pt 1): 132577, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38795887

RESUMO

Staphylococcus aureus is a pathogen widely involved in wound infection due to its ability to release several virulence factors that impair the skin healing process, as well as its mechanism of drug resistance. Herein, sodium alginate and chitosan were combined to produce a hydrogel for topical delivery of neomycin to combat S. aureus associated with skin complications. The hydrogel was formulated by combining sodium alginate (50 mg/mL) and chitosan (50 mg/mL) solutions in a ratio of 9:1 (HBase). Neomycin was added to HBase to achieve a concentration of 0.4 mg/mL (HNeo). The incorporation of neomycin into the product was confirmed by scanning electron microscopy, FTIR and TGA analysis. The hydrogels produced are homogeneous, have a high swelling capacity, and show biocompatibility using erythrocytes and fibroblasts as models. The formulations showed physicochemical and pharmacological stability for 60 days at 4 ± 2 °C. HNeo totally inhibited the growth of S. aureus after 4 h. The antimicrobial effects were confirmed using ex vivo (porcine skin) and in vivo (murine) wound infection models. Furthermore, the HNeo-treated mice showed lower severity scores than those treated with HBase. Taken together, the obtained results present a new low-cost bioproduct with promising applications in treating infected wounds.


Assuntos
Alginatos , Antibacterianos , Quitosana , Hidrogéis , Neomicina , Staphylococcus aureus , Quitosana/química , Quitosana/farmacologia , Alginatos/química , Alginatos/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Camundongos , Neomicina/farmacologia , Neomicina/química , Neomicina/administração & dosagem , Antibacterianos/farmacologia , Antibacterianos/química , Infecções Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/patologia , Portadores de Fármacos/química , Pele/efeitos dos fármacos , Pele/microbiologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-38593207

RESUMO

Wounds infected with bacteria, if left untreated, have the potential to escalate into life-threatening conditions, such as sepsis, which is characterized by widespread inflammation and organ damage. A comprehensive approach to treating bacterial-infected wounds, encompassing the control of bacterial infection, biofilm eradication, and inflammation regulation, holds significant importance. Herein, a microneedle (MN) patch (FM@ST MN) has been developed, with silk fibroin (SF) and tannic acid-based hydrogel serving as the matrix. Encapsulated within the MNs are the AIEgen-based activatable probe (FQ-H2O2) and the NLRP3 inhibitor MCC950, serving as the optical reporter/antibacterial agent and the inflammation regulator, respectively. When applied onto bacterial-infected wounds, the MNs in FM@ST MN penetrate bacterial biofilms and gradually degrade, releasing FQ-H2O2 and MCC950. The released FQ-H2O2 responds to endogenously overexpressed reactive oxygen species (H2O2) at the wound site, generating a chromophore FQ-OH which emits noticeable NIR-II fluorescence and optoacoustic signals, enabling real-time imaging for outcome monitoring; and this chromophore also exhibits potent antibacterial capability due to its dual positive charges and shows negligible antibacterial resistance. However, the NLRP3 inhibitor MCC950, upon release, suppresses the activation of NLRP3 inflammasomes, thereby mitigating the inflammation triggered by bacterial infections and facilitating wound healing. Furthermore, SF in FM@ST MN aids in tissue repair and regeneration by promoting the proliferation of epidermal cells and fibroblasts and collagen synthesis. This MN system, free from antibiotics, holds promise as a solution for treating and monitoring bacterially infected wounds without the associated risk of antimicrobial resistance.

6.
Pharmaceutics ; 16(3)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38543221

RESUMO

Bacterial infections are major problems in wound care due to their impact on the retarded process of wound healing, leading to chronic wounds. Most of the presently utilized wound dressing products exhibit poor antimicrobial properties. Wound dressings formulated from chitosan have been reported to be effective for treating infected wounds, resulting from the antibacterial properties of chitosan. The antibacterial properties of chitosan-based wound dressings can be further enhanced by incorporating metallic nanoparticles into them, such as silver, zinc, titanium, etc. The incorporation of silver nanoparticles into chitosan-based wound dressings has been widely explored in the design of antimicrobial wound dressings. The incorporation of silver nanoparticles into chitosan-based wound dressings promotes accelerated wound-healing processes due to enhanced antimicrobial activity. The accelerated wound healing by these metal-based nanoparticles is via the regulation of re-epithelialization and inflammation without affecting the viability of normal cells. However, there have been few reports that evaluate these wound dressings in infectious animal models to prove their efficacy. The in vivo toxicity of silver nanoparticles still needs to be addressed, revealing the need for further preclinical and clinical trials. The fabrication of wound dressings incorporated with silver nanoparticles has not been fully explored, especially for wounds requiring immediate treatment. The possible interactions between silver nanoparticles and chitosan scaffolds that result in synergistic effects still need to be understood and studied. This review provides a comprehensive report on the preclinical outcomes of chitosan wound dressing materials loaded with silver nanoparticles for managing infected wounds.

7.
Carbohydr Polym ; 332: 121912, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38431415

RESUMO

Bacterial-infected wounds present a significant challenge in the medical field, posing a severe threat to public health. Traditional wound dressings have limited efficacy in treating bacterial-infected wounds, and antibiotics suffer from cytotoxicity and drug resistance. Consequently, an urgent requirement exists for developing multifunctional wound dressings capable of providing superior antimicrobial activity and expediting wound repair. In recent years, chitosan-based natural polysaccharide hydrogels have garnered attention for their biocompatibility, antimicrobial properties, and ability to aid in hemostasis. This study presents the development of a multi-functional, bi-dynamic network hydrogel for the treatment of wounds infected with bacteria. The hydrogel consists of a backbone of chitosan grafted with chlorogenic acid (CA-ECS), oxidized pullulan polysaccharides (OP), and zinc ions (Zn2+). The CA-ECS/OP/Zn2+ hydrogel displayed strong adhesion, good injectability, and high mechanical strength and was biodegradable and biocompatible. Furthermore, adding Zn2+ and CA enhanced the hydrogel's mechanical properties and antioxidant and antimicrobial activities. In a rat model of full-thickness skin wounds infected with S. aureus, the CA-ECS/OP/Zn2+ hydrogel demonstrated great anti-inflammatory, angiogenic, and folliculogenic properties, resulting in accelerated wound healing. The CA-ECS/OP/Zn2+ hydrogel has great potential for treating bacterial-infected wounds.


Assuntos
Quitosana , Polifenóis , Animais , Ratos , Hidrogéis , Staphylococcus aureus , Polissacarídeos/farmacologia , Metais , Antibacterianos/farmacologia
8.
Small ; : e2312253, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501846

RESUMO

Chronic wounds of significant severity and acute injuries are highly vulnerable to fungal infections, drastically impeding the expected wound healing trajectory. The clinical use of antifungal therapeutic drug is hampered by poor solubility, high toxicity and adverse reactions, thereby necessitating the urgent development of novel antifungal therapy strategy. Herein, this study proposes a new strategy to enhance the bioactivity of small-molecule antifungal drugs based on multifunctional metal nanozyme engineering, using amphotericin B (AmB) as an example. AmB-decorated gold nanoparticles (AmB@AuNPs) are synthesized by a facile one-pot reaction strategy, and the AmB@AuNPs exhibit superior peroxidase (POD)-like enzyme activity, with maximal reaction rates (Vmax ) 3.4 times higher than that of AuNPs for the catalytic reaction of H2 O2 . Importantly, the enzyme-like activity of AuNPs significantly enhanced the antifungal properties of AmB, and the minimum inhibitory concentrations of AmB@AuNPs against Candida albicans (C. albicans) and Saccharomyces cerevisiae (S. cerevisiae) W303 are reduced by 1.6-fold and 50-fold, respectively, as compared with AmB alone. Concurrent in vivo studies conducted on fungal-infected wounds in mice underscored the fundamentally superior antifungal ability and biosafety of AmB@AuNPs. The proposed strategy of engineering antifungal drugs with nanozymes has great potential for enhanced therapy of fungal infections and related diseases.

9.
Adv Sci (Weinh) ; 11(17): e2306602, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38350733

RESUMO

Wounds infected with multidrug-resistant (MDR) bacteria are increasingly threatening public health and challenging clinical treatments because of intensive bacterial colonization, excessive inflammatory responses, and superabundant oxidative stress. To overcome this malignant burden and promote wound healing, a multifunctional cryogel (HA/TA2/KR2) composed of hyaluronic acid (HA), tannic acid (TA), and KR-12 peptides is designed. The cryogel exhibited excellent shape-memory properties, strong absorption performance, and hemostatic capacity. In vitro experiments demonstrated that KR-12 in the cryogel can be responsively released by stimulation with hyaluronidase produced by bacteria, reaching robust antibacterial activity against Escherichia coli (E. coli), MDR Pseudomonas aeruginosa (MDR-PA), and methicillin-resistant Staphylococcus aureus (MRSA) by disrupting bacterial cell membranes. Furthermore, the synergetic effect of KR-12 and TA can efficiently scavenge ROS and decrease expression of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α & interleukin (IL)-6), as well as modulate the macrophage phenotype toward the M2 type. In vivo animal tests indicated that the cryogel can effectively destroy bacteria in the wound and promote healing process via accelerating angiogenesis and re-epithelialization. Proteomic analysis revealed the underlying mechanism by which the cryogel mainly reshaped the infected wound microenvironment by inhibiting the Nuclear factor kappa B (NF-κB) signaling pathway and activating the Janus kinase-Signal transducer and activator of transcription (JAK-STAT6) signaling pathway. Therefore, the HA/TA2/KR2 cryogel is a promising dressing candidate for MDR bacteria-infected wound healing.


Assuntos
Antibacterianos , Criogéis , Modelos Animais de Doenças , Hialuronoglucosaminidase , Espécies Reativas de Oxigênio , Cicatrização , Animais , Camundongos , Antibacterianos/farmacologia , Criogéis/farmacologia , Criogéis/química , Escherichia coli/efeitos dos fármacos , Ácido Hialurônico/farmacologia , Hialuronoglucosaminidase/metabolismo , Inflamação/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Camundongos Endogâmicos BALB C
10.
Wound Repair Regen ; 32(3): 301-313, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38308577

RESUMO

Bacterial wound infection has emerged as a pivotal threat to human health worldwide, and the situation has worsened owing to the gradual increase in antibiotic-resistant bacteria caused by the improper use of antibiotics. To reduce the use of antibiotics and avoid the increase in antibiotic-resistant bacteria, researchers are increasingly paying attention to  photodynamic therapy, which uses light to produce reactive oxygen species to kill bacteria. Treating bacteria-infected wounds by photodynamic therapy requires fixing the photosensitizer (PS) at the wound site and maintaining a certain level of wound humidity. Hydrogels are materials with a high water content and are well suited for fixing PSs at wound sites for antibacterial photodynamic therapy. Therefore, hydrogels are often loaded with PSs for treating bacteria-infected wounds via antibacterial photodynamic therapy. In this review, we systematically summarised the antibacterial mechanisms and applications of PS-loaded hydrogels for treating bacteria-infected wounds via photodynamic therapy. In addition, the recent  studies and the research status progresses of novel antibacterial hydrogels are discussed. Finally, the challenges and future prospects of PS-loaded hydrogels are reviewed.


Assuntos
Antibacterianos , Bandagens , Hidrogéis , Fármacos Fotossensibilizantes , Infecção dos Ferimentos , Humanos , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Hidrogéis/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia
11.
Int Wound J ; 21(1): e14628, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38272817

RESUMO

High-grade gliomas (HGGs) may be amenable to the neurosurgical technique known as laser interstitial thermal therapy (LITT), which delivers thermal energy to interstitial brain injuries and wounds with pinpoint accuracy. The purpose of this extensive meta-analysis was to evaluate the effects of LITT on wound complications among patients who have brain tumours. Diverse conclusions emerge from a systematic review of pertinent studies, necessitating a comprehensive examination. The meta-analysis, performed utilizing the meta library provided by the R package meta, reveals an initial significant overall effect (RR: -2.1262, 95% CI [-2.7466, -1.5059], p < 0.0001) accompanied by considerable heterogeneity among studies (I2 = 61.13%). Following analyses that specifically examined the incidence of wounds, a complex correlation was found (RR: 0.0471, 95% CI [0.0264, 0.0842], p < 0.0001), indicating that LITT has a discernible but insignificant effect on the occurrence of wounds. Although the meta-analysis emphasizes a notable decrease in wound complications subsequent to LITT treatment, additional research is warranted due to constraints in standardized reporting, data accessibility, and small sample sizes. The results of this study underscore the need for exhaustive protocols to analyse wound complications in patients with brain tumours undergoing LITT.


Assuntos
Neoplasias Encefálicas , Hipertermia Induzida , Terapia a Laser , Humanos , Neoplasias Encefálicas/etiologia , Neoplasias Encefálicas/cirurgia , Hipertermia Induzida/efeitos adversos , Hipertermia Induzida/métodos , Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , Lasers , Cicatrização
13.
Regen Biomater ; 11: rbad110, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38173767

RESUMO

For the treatment of MRSA-infected wounds, the spatiotemporally sequential delivery of antibacterial and anti-inflammatory drugs is a promising strategy. In this study, ROS-responsive HA-PBA/PVA (HPA) hydrogel was prepared by phenylborate ester bond cross-linking between hyaluronic acid-grafted 3-amino phenylboronic acid (HA-PBA) and polyvinyl alcohol (PVA) to achieve spatiotemporally controlled release of two kinds of drug to treat MRSA-infected wound. The hydrophilic antibiotic moxifloxacin (M) was directly loaded in the hydrogel. And hydrophobic curcumin (Cur) with anti-inflammatory function was first mixed with Pluronic F127 (PF) to form Cur-encapsulated PF micelles (Cur-PF), and then loaded into the HPA hydrogel. Due to the different hydrophilic and hydrophobic nature of moxifloxacin and Cur and their different existing forms in the HPA hydrogel, the final HPA/M&Cur-PF hydrogel can achieve different spatiotemporally sequential delivery of the two drugs. In addition, the swelling, degradation, self-healing, antibacterial, anti-inflammatory, antioxidant property, and biocompatibility of hydrogels were tested. Finally, in the MRSA-infected mouse skin wound, the hydrogel-treated group showed faster wound closure, less inflammation and more collagen deposition. Immunofluorescence experiments further confirmed that the hydrogel promoted better repair by reducing inflammation (TNF-α) and promoting vascular (VEGF) regeneration. In conclusion, this HPA/M&Cur-PF hydrogel that can spatiotemporally sequential deliver antibacterial and anti-inflammatory drugs showed great potential for the repair of MRSA-infected skin wounds.

14.
Int J Biol Macromol ; 254(Pt 1): 127549, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37863134

RESUMO

This study was conducted to evaluate the effects of alginate-chitosan/titanium oxide/geraniol (Alg-Csn/TiO2@GRL nanosphere) nanospheres hydrogels on the healing process of the wounds infected with Acinetobacter baumannii and Streptococcus pyogenes bacteria. The nanospheres were successfully synthesized and their physicochemical properties such as DLS, FTIR, FE-SEM, TEM, XRD and also their safety and in-vitro antibacterial activity were assessed and confirmed. Following induction of the infected wounds, the mice were treated with s base ointment (Control), mupirocin® as standard control group and also hydrogels prepared from Alg-Csn@GRL, Alg-Csn/TiO2 and Alg-Csn/TiO2@GRL. Wound contraction, total bacterial count, expression of bFGF, VEGF, IGF-1, CD68 and COL-1 A, iNOS and eNOS were measured. The results showed the treatment of wounds with Alg-Csn/TiO2@GRL hydrogels significantly accelerated wound contraction, decreased total bacterial count and reduced the expressions of CD68, iNOS and eNOS and increased the expressions of VEGF, bFGF, IGF-1 and COL-1 A compared with other groups. It can be concluded that Alg-Csn/TiO2@GRL hydrogels expedite the wound healing process by their effects on bacteria and subsequently inflammation and increasing the expression of proliferative genes. The Alg-Csn/TiO2@GRL hydrogel can be utilized in combination with other agents for the treatment of infected wounds after future clinical studies.


Assuntos
Acinetobacter baumannii , Quitosana , Nanosferas , Camundongos , Animais , Quitosana/química , Fator de Crescimento Insulin-Like I/farmacologia , Streptococcus pyogenes , Hidrogéis/química , Alginatos/química , Fator A de Crescimento do Endotélio Vascular/farmacologia , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química
15.
Curr Drug Deliv ; 21(5): 753-762, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37183469

RESUMO

BACKGROUND: Bacterial infection can delay wound healing and is therefore a major threat to public health. Although various strategies have been developed to treat bacterial infections, antibiotics remain the best option to combat infections. The inclusion of growth factors in the treatment approach can also accelerate wound healing. The co-delivery of antibiotics and growth factors for the combined treatment of wounds needs further investigation. OBJECTIVE: Here we aimed to develop antibiotic and growth factor co-loaded nanoparticles (NPs) to treat Staphylococcus aureus-infected wounds. METHODS: By using our previously prepared reactive oxygen species-responsive material (Oxi-αCD), roxithromycin (ROX)-loaded NPs (ROX/Oxi-αCD NPs) and recombinant human epidermal growth factor (rhEGF)/ROX co-loaded NPs (rhEGF/ROX/Oxi-αCD NPs) were successfully fabricated. The in vivo efficacy of this prepared nanomedicine was evaluated in mice with S. aureus-infected wounds. RESULTS: ROX/Oxi-αCD NPs and rhEGF/ROX/Oxi-αCD NPs had a spherical structure and their particle sizes were 164 ± 5 nm and 190 ± 8 nm, respectively. The in vitro antibacterial experiments showed that ROX/Oxi-αCD NPs had a lower minimum inhibitory concentration than ROX. The in vivo animal experiments demonstrated that rhEGF/ROX/Oxi-αCD NPs could significantly accelerate the healing of S. aureus-infected wounds as compared to the free ROX drug and ROX/Oxi-αCD NPs (P < 0.05). CONCLUSION: ROX and rhEGF co-loaded NPs can effectively eliminate bacteria in wounds and accelerate wound healing. Our present work could provide a new strategy to combat bacteria-infected wounds.


Assuntos
Nanopartículas , Roxitromicina , Humanos , Camundongos , Animais , Roxitromicina/farmacologia , Roxitromicina/uso terapêutico , Espécies Reativas de Oxigênio , Staphylococcus aureus , Fator de Crescimento Epidérmico/farmacologia , Fator de Crescimento Epidérmico/uso terapêutico , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias
16.
Mater Today Bio ; 23: 100875, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38075251

RESUMO

Complete and rapid healing of infected skin wounds remains a challenge in current clinical treatment. In this study, we prepared a self-healing injectable CK hydrogel by crosslinking two natural polysaccharides, carboxymethyl chitosan and oxidized konjac glucomannan, based on the Schiff base bond. To enhance the biological function of the hydrogel, we multi-functionalized hydrogen by loading it with berberine (BBR) and stem cell-derived exosomes (Exo), forming a composite hydrogel, CK@BBR&Exo, which could be injected directly into the wound through a needle and adhered to the wound. Furthermore, the self-healing properties of CK@BBR&Exo increased its usefulness and service life. Additionally, the drug-loaded CK@BBR&Exo hydrogel was versatile, inhibiting bacterial growth, regulating the inflammatory response, and promoting neovascularization in infected skin wounds, thus achieving the rapid healing of infected skin wounds. These results suggest that the CK@BBR&Exo-injectable self-healing hydrogel is an ideal dressing for treating infected skin wounds.

17.
Small ; : e2307256, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38018326

RESUMO

Removal of invasive bacteria is critical for proper wound healing. This task is challenging because these bacteria can trigger intense oxidative stress and gradually develop antibiotic resistance. Here, the use of a multienzyme-integrated nanocatalytic platform is reported for efficient bacterial clearance and mitigation of inflammatory responses, constructed by physically adsorbing natural superoxide dismutase (SOD), in situ reduction of gold nanoparticles (Au NPs), and incorporation of a DNAzyme on 2D NiCoCu metal-organic frameworks (DNAzyme/SOD/Au@NiCoCu MOFs, termed DSAM), which can adapt to infected wounds. O2 and H2 O2 replenishment is achieved and alleviated the hypoxic microenvironment using the antioxidant properties of SOD. The H2 O2 produced during the reaction is decomposed by peroxidase (POD)-like activity enhanced by Au NPs and DNAzyme, releasing highly toxic hydroxyl radicals (•OH) to kill the bacteria. In addition, it possesses glutathione peroxidase (GPx)-like activity, which depletes GSH and prevents •OH loss. Systematic antimicrobial tests are performed against bacteria using this multienzyme-integrated nanoplatform. A dual-mode strategy involving natural enzyme-enhanced antioxidant capacity and artificial enzyme-enhanced •OH release to develop an efficient and novel enzyme-integrated therapeutic platform is integrated.

18.
Int J Nanomedicine ; 18: 4663-4679, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37605733

RESUMO

Background: Multidrug-resistant staphylococcus aureus infected wounds can lead to nonhealing, systemic infections, and even death. Although advanced dressings are effective in protecting, disinfecting, and maintaining moist microenvironments, they often have limitations such as single functionality, inadequate drug release, poor biosafety, or high rates of drug resistance. Methods: Here, a novel wound dressing comprising glycyrrhizic acid (GA) and tryptophan-sorbitol carbon quantum dots (WS-CQDs) was developed, which exhibit synergistic and long-lasting antibacterial and anti-inflammatory effects. We investigated the characterization, mechanical properties, synergistic antibacterial effects, sustained-release properties, and cytotoxicity of GA/WS-CQDs hydrogels in vitro. Additionally, we performed transcriptome sequence analysis to elucidate the antibacterial mechanism. Furthermore, we evaluated the biosafety, anti-inflammatory effects, and wound healing ability of GA/WS-CQDs dressings using an in vivo mouse model of methicillin-resistant staphylococcus aureus (MRSA)-infected wounds. Results: The prepared GA/WS-CQDs hydrogels demonstrated superior anti-MRSA effects compared to common antibiotics in vitro. Furthermore, the sustained release of WS-CQDs from GA/WS-CQDs hydrogels lasted for up to 60 h, with a cumulative release of exceeding 90%. The sustained-released WS-CQDs exhibited excellent anti-MRSA effects, with low drug resistance attributed to DNA damage and inhibition of bacterial biofilm formation. Notably, in vivo experiments showed that GA/WS-CQDs dressings reduced the expression of inflammatory factors (TNF-α, IL-1ß, and IL-6) and significantly promoted the healing of MRSA-infected wounds with almost no systemic toxicity. Importantly, the dressings did not require replacement during the treatment process. Conclusion: These findings emphasize the high suitability of GA/WS-CQDs dressings for MRSA-infected wound healing and their potential for clinical translation.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Staphylococcus aureus , Animais , Camundongos , Antibacterianos/farmacologia , Bandagens , Ácido Glicirrízico , Hidrogéis/farmacologia , Anti-Inflamatórios
19.
Pharmaceutics ; 15(7)2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37514062

RESUMO

Bacterial infections are a constant challenge in the management of acute and chronic wounds. Chronic wounds, such as diabetic foot ulcers, have increased significantly in the last few years due to the rise of an aging population. A better understanding of the infectious pathophysiological mechanisms is urgently needed along with new options for the treatment of wound infections and wound-healing disorders. New advances in the preparation of biocompatible dressing materials that can be loaded with antimicrobial drugs may improve the topical treatment of infected wounds. In this study, we investigated the antimicrobial activity of polyvinylpyrrolidone (PVP) foils loaded with ciprofloxacin (Cipro-foils) in the presence of acetic acid as a co-solvent. We used ex vivo human wounds that were infected with two bacterial strains: methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (PAO1). The effectiveness of the treatment was demonstrated by the quantification of the living bacteria extracted from the wound and the detection of released immunological mediators in skin extracts and in the skin culture media. We found that Cipro-foils effectively treated the infection with both PAO1 and MRSA. Other than PAO1, MRSA had no lytic activity toward skin proteins. MRSA infections increased cytokines' expression and release. Interestingly, treatment with Cipro-foils could partially counteract these effects.

20.
Proteomics Clin Appl ; 17(4): e2200069, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37062883

RESUMO

PURPOSE: Helcococcus kunzii is a skin commensal, Gram-positive bacterium, mostly isolated from infected chronic wounds. This opportunistic pathogen is usually co-isolated with Staphylococcus aureus. The present dataset explores the production and secretion of H. kunzii bacterial virulence interacting proteins in a growth medium mimicking chronic wounds in exponential and stationary growth phases. EXPERIMENTAL DESIGN: The H. kunzii cellular proteome and exoproteome were assessed by analyzing three biological replicates per condition tested. Samples were analyzed using a Q-Exactive HF mass spectrometer. Comparative and functional analyses were performed to profile the identified protein set. RESULTS: The H. kunzii's cellular proteome encompassed 969 proteins, among which 64 and 53 were specifically identified in the exponential and stationary phase of growth, respectively. Its exoproteome comprised 58 proteins, among which 16 and 14 were characteristic of each growth stage. Metabolic differences between the two phases of growth are discussed. Besides, the production of previously shortlisted and novel putative H. kunzii targets involved in modulating the virulence of S. aureus is investigated. CONCLUSION AND CLINICAL RELEVANCE: This work, pioneering the study of H. kunzii physiology in a chronic wound-like environment, should assist future research on this opportunistic pathogen and the search for innovative approaches for wound management.


Assuntos
Diabetes Mellitus , Pé Diabético , Cocos Gram-Positivos , Humanos , Proteoma/genética , Staphylococcus aureus , Proteômica
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